Nef-Mediated CD3-TCR Downmodulation Dampens Acute Inflammation and Promotes SIV Immune Evasion.

ABSTRACT: The inability of Nef to downmodulate the CD3-T cell receptor (TCR) complex distinguishes HIV-1 from other primate lentiviruses and may contribute to its high virulence. However, the role of this Nef function in virus-mediated immune activation and pathogenicity remains speculative. Here, we selectively disrupted this Nef activity in SIV_mac239 and analyzed the consequences for the virological, immunological, and clinical outcome of infection in rhesus macaques. The inability to downmodulate CD3-TCR does not impair viral replication during acute infection but is associated with increased immune activation and antiviral gene expression. Subsequent early reversion in three of six animals suggests strong selective pressure for this Nef function and is associated with high viral loads

SUBMITTER: Joas S 

PROVIDER: S-EPMC7052273 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature